A Simplified Model of Adenine-Induced Chronic Kidney Disease Using SKH1 Mice.

Commonly used adenine-induced chronic kidney disease (CKD) murine models often employ C57BL/6 mice; however, this strain has inherent limitations due to its natural resistance to developing key pathological features of CKD, such as tubulointerstitial fibrosis and inflammation. There have been attempts to overcome these barriers by using multiple concentrations of adenine-supplemented diets or by performing prolonged experiments up to 20 weeks. Here, we demonstrate that SKH1 Elite mice develop clinically relevant CKD phenotypes (e.

Aerosolized Harmful Algal Bloom Toxin Microcystin-LR Induces Type 1/Type 17 Inflammation of Murine Airways.

Harmful algal blooms are increasing globally and pose serious health concerns releasing cyanotoxins. Microcystin-LR (MC-LR), one of the most frequently produced cyanotoxins, has recently been detected in aerosols generated by the normal motions of affected bodies of water. MC-LR aerosol exposure has been linked to a pro-inflammatory influence on the airways of mice; however, little is understood about the underlying mechanism or the potential consequences.

Time-resolved interactome profiling deconvolutes secretory protein quality control dynamics.

Many cellular processes are governed by protein-protein interactions that require tight spatial and temporal regulation. Accordingly, it is necessary to understand the dynamics of these interactions to fully comprehend and elucidate cellular processes and pathological disease states. To map de novo protein-protein interactions with time resolution at an organelle-wide scale, we developed a quantitative mass spectrometry method, time-resolved interactome profiling (TRIP).

Malignant hyperthermia in a paediatric patient; managed successfully without dantrolene: a case report.

Introduction: Malignant hyperthermia (MH) is a potentially life-threatening pharmacogenetic syndrome triggered by volatile anaesthetics, succinylcholine, and stress such as vigorous exercise.

Case Presentation: The authors describe a case of an 8-year-old male who presented with classical symptoms of MH after induction of general anaesthesia and symptomatic treatment was done successfully due to the unavailability of Dantrolene.

Discussion: Definitive diagnosis of MH can be done based on a contracture test in fresh muscle biopsy in the presence of halothane and caffeine.

Elexacaftor/VX-445-mediated CFTR interactome remodeling reveals differential correction driven by mutation-specific translational dynamics.

Cystic fibrosis (CF) is one of the most prevalent lethal genetic diseases with over 2000 identified mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Pharmacological chaperones such as lumacaftor (VX-809), tezacaftor (VX-661), and elexacaftor (VX-445) treat mutation-induced defects by stabilizing CFTR and are called correctors. These correctors improve proper folding and thus facilitate processing and trafficking to increase the amount of functional CFTR on the cell surface.

Differential Effects of the Processed and Unprocessed Garlic ( L.) Ethanol Extracts on Neuritogenesis and Synaptogenesis in Rat Primary Hippocampal Neurons.

Garlic ( L.) is an aromatic herb known for its culinary and medicinal uses for centuries. Both unprocessed (white) and processed (black) garlic are known to protect against the pathobiology of neurological disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), which has been attributed to their anti-inflammatory and antioxidant properties.

N-Acetylglucosamine Kinase-Small Nuclear Ribonucleoprotein Polypeptide N Interaction Promotes Axodendritic Branching in Neurons via Dynein-Mediated Microtubule Transport.

N-acetylglucosamine kinase (NAGK) has been identified as an anchor protein that facilitates neurodevelopment with its non-canonical structural role. Similarly, small nuclear ribonucleoprotein polypeptide N (SNRPN) regulates neurodevelopment and cognitive ability. In our previous study, we revealed the interaction between NAGK and SNRPN in the neuron.

Neuronal Differentiation and Outgrowth Effect of Thymol in Seed Extract via BDNF/TrkB Signaling Pathway in Prenatal Maternal Supplementation and Primary Hippocampal Culture.

Reviving the neuronal functions in neurodegenerative disorders requires the promotion of neurite outgrowth. Thymol, which is a principal component of seed extract (TASE), is reported to have neuroprotective effects. However, the effects of thymol and TASE on neuronal differentiation and outgrowth are yet to be studied.

Thymol in Trachyspermum ammi seed extract exhibits neuroprotection, learning, and memory enhancement in scopolamine-induced Alzheimer's disease mouse model.

Several reports have stated the neuroprotective and learning/memory effects of Tachyspermum ammi seed extract (TASE) and its principal component thymol; however, little is known about its underlying molecular mechanisms and neurogenesis potential. This study aimed to provide insights into TASE and a thymol-mediated multifactorial therapeutic approach in a scopolamine-induced Alzheimer's disease (AD) mouse model. TASE and thymol supplementation significantly reduced oxidative stress markers such as brain glutathione, hydrogen peroxide, and malondialdehyde in mouse whole brain homogenates.

Elexacaftor/VX-445-mediated CFTR interactome remodeling reveals differential correction driven by mutation-specific translational dynamics.

Cystic fibrosis (CF) is one of the most prevalent lethal genetic diseases with over 2000 identified mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Pharmacological chaperones such as Lumacaftor (VX-809), Tezacaftor (VX-661) and Elexacaftor (VX-445) treat mutation-induced defects by stabilizing CFTR and are called correctors. These correctors improve proper folding and thus facilitate processing and trafficking to increase the amount of functional CFTR on the cell surface.

Functional Characterization of a Regiospecific Sugar--Methyltransferase from .

Methyltransferases transfer a methyl group to a diverse group of natural products, thus providing structural diversity, stability, and altered pharmacological properties to the molecules. A limited number of regiospecific sugar--methyltransferases are functionally characterized. Thus, discovery of such an enzyme could solve the difficulties of biological production of methoxy derivatives of glycosylated molecules.

Inhibition Mechanism of Components Isolated from Branches on Diabetes and Diabetic Complications via Experimental and Molecular Docking Analyses.

Previously, we reported the anti-diabetic effect of root bark and the compounds therein. In our continuous study of other parts of this plant, the ability of the branch of to inhibit α-glucosidase, protein tyrosine phosphatase 1B (PTP1B), and advanced glycation end products (AGEs) formation was evaluated. Moreover, there are no previous studies that have performed enzyme kinetics and molecular docking analyses, along with assessments of peroxynitrite (ONOO) inhibitory activities.

Black Cumin ( L.): A Comprehensive Review on Phytochemistry, Health Benefits, Molecular Pharmacology, and Safety.

Mounting evidence support the potential benefits of functional foods or nutraceuticals for human health and diseases. Black cumin ( L.), a highly valued nutraceutical herb with a wide array of health benefits, has attracted growing interest from health-conscious individuals, the scientific community, and pharmaceutical industries.

Potential roles of natural products in the targeting of proteinopathic neurodegenerative diseases.

Defective proteostasis is associated with the gradual accumulations of misfolded proteins and is a hallmark of many age-associated neurodegenerative diseases. In the aged brain, maintenance of the proteostasis network presents a substantial challenge, and its loss contributes to the onset and progression of neurological diseases associated with cognitive decline due to the generation of toxic protein aggregates, a process termed 'proteinopathy'. Emerging evidence suggests that reversing proteinopathies by boosting proteostasis might provide an effective means of preventing neurodegeneration.

Centella asiatica promotes early differentiation, axodendritic maturation and synaptic formation in primary hippocampal neurons.

Background: Centella asiatica is a 'medhya-rasayana (nootrophic or memory booster)' herb that has been indicated in Ayurveda for improving memory function and treating dementia disorders. Although the neuroprotective effects of C. asiatica have been reported in earlier studies, the information on whether this nootropic herb could promote early differentiation and development of axon and dendrites in primary hippocampal neurons is currently limited.

Inducible clindamycin resistance and genes in in school children in Kathmandu, Nepal.

Aim: Resistance to methicillin and Macrolide-Lincosamide and Streptogramins B and their association with genes in are unknown in Nepal.

Materials & Methods: Nonduplicate nasal swabs from 160 school children were collected from April to September 2018 and processed using standard microbiological procedures.

Results: Out of 160 samples, 64 (40%) were in which 17 (26.

Emerging potential of cannabidiol in reversing proteinopathies.

The aberrant accumulation of disease-specific protein aggregates accompanying cognitive decline is a pathological hallmark of age-associated neurological disorders, also termed as proteinopathies, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and multiple sclerosis. Along with oxidative stress and neuroinflammation, disruption in protein homeostasis (proteostasis), a network that constitutes protein surveillance system, plays a pivotal role in the pathobiology of these dementia disorders. Cannabidiol (CBD), a non-psychotropic phytocannabinoid of Cannabis sativa, is known for its pleiotropic neuropharmacological effects on the central nervous system, including the ability to abate oxidative stress, neuroinflammation, and protein misfolding.

Congenital Microphthalmia with Intraorbital Cyst: A Rare Case Report.

Microphthalmia is considered to be the most common congenital malformation of the eye after congenital cataract. However, its association with intraorbital cyst is considered to be very rare. Most of the lesions are still misdiagnosed as orbital tumor and teratomas as there is a general paucity of data reported in literature.

Correlates of Biochemical Markers of Bone turnover among Post-Menopausal Women.

Introduction: Bone turnover leading to osteoporosis and poor quality of life is common during post-menopausal period. Study of bone turnover markers that contribute to non-invasive assessment of bone-metabolic disorders holds an important area of research in low income country like Nepal. This study aimed to examine the correlates of bone turnover markers in post-menopausal women in tertiary level of health care center of Nepal.

Comparative Genomics of Nitrogen Cycling Pathways in Bacteria and Archaea.

Despite the explosion of metagenomic sequencing data, using -omics data to predict environmental biogeochemistry remains a challenge. One or a few genes (referred to as marker genes) in a metabolic pathway of interest in meta-omic data are typically used to represent the prevalence of a biogeochemical reaction. This approach often fails to demonstrate a consistent relationship between gene abundance and an ecosystem process rate.

Prevalence and Factors Associated with Microalbuminuria among Type 2 Diabetic Patients : A Hospital Based Study.

Introduction: Microalbuminuria is the earliest clinical evidence of diabetic nephropathy. However, prevalence and associated factors with microalbuminuria among type 2 diabetic patients has been understudied area of research in Nepalese context. This study aimed to determine the prevalence and factors associated with microalbuminuria among type 2 diabetic patients.

Effect of Maternal Socio-demographic Factors and Child Feeding Practice on Wasting Among Under Five Years Children in Slum Area of Rupandehi District in Nepal.

Introduction: Childhood wasting although well studied elsewhere, it has not been well understood about in slum area of Nepal. This study aimed to assess effect of socio-demographic factors and child feeding practice in the determination of wasting among the children under five years of age in slum area of Nepal.

Methods: A community based cross-sectional study was performed among 150 children under five years of age from the slum area of Nepal between 1st January and 28th February 2013 using simple random sampling techniques.

A Study on Variations of Nutrient Foramen of Humerus with its Clinical Implications.

Background Nutrient foramen is an opening into shaft of humerus which gives passage to the blood vessels of medullary cavity. The knowledge of nutrient foramen is important in surgical procedures like bone grafting and more recently in microsurgical vascularized bone transplantation. Objective To determine the number, location and direction of nutrient foramen and whether the nutrient foramens obey the rule of ossification, that is directed away from the growing end of the bone or not.